CGS 21680 is a chemical compound that acts as a selective agonist for both adenosine and its A2A receptor, demonstrating a binding affinity (K i) of 27 nM.

CGS21680 notably increases the levels of CD39 and CD73 expression and enhances the breakdown of adenosine triphosphate (ATP) into adenosine [1]. While CGS21680 at a concentration of 10 nM demonstrates minimal survival activity independently, this activity is substantially boosted when combined with the phosphodiesterase inhibitor, IBMX. The enhancement of motoneuron survival by CGS21680 is attributed to the combined influence of the adenylate cyclase-cAMP-PKA pathway and the transactivation of neurotrophin receptors [4].

CGS21680 (1 mg/kg/i.p.) administration exacerbates experimental autoimmune neuritis (EAN) in bovine peripheral myelin-induced Lewis rats by lowering CD4+ Foxp3+ T cells and raising CD4+ CXCR5+ T cells, B cells, dendritic cells, and antigen-specific autoantibodies, likely due to its suppression of IL-2. At 0.1 mg/kg (i.p.), CGS21680 temporarily increases heart rate without affecting blood pressure in rats, while at 0.01 mg/kg, it has no effect on heart rate or blood pressure. Post-transient middle cerebral artery occlusion (MCAo), CGS21680 (both doses) protects against neurological deficits for up to 7 days, reduces microgliosis and astrogliosis, and improves myelin organization and cytoarchitecture in the ischemic cortex and striatum. Two days post-MCAo, it reduces granulocyte infiltration in ischemic tissue.